Autologous stem cell rescue recipient with neutrophil tissue delivery detected prior to blood engraftment: A case report

Abstract Neutrophil recovery after autologous hematopoietic cell transplantation (ASCT) is affirmed with achievement of an absolute neutrophil count (ANC) of ≥500/µL. There is growing evidence that neutrophils may be observed despite undetectable peripheral ANC counts following autologous hematopoietic cell transplant and are preferentially delivered to sites of inflammation. We report an interesting case that confirms neutrophil tissue delivery to the skin two days prior to evidence of blood engraftment after an ASCT.


INTRODUCTION
Myeloid engraftment is defined as an absolute neutrophil count (ANC) of ≥500/µL and is often achieved within 14 days of transplant [1,2].
Potential methods of earlier identification of marrow recovery have been explored, although their clinical use is not yet widespread. We report a compelling case that demonstrates neutrophil tissue delivery, confirmed by skin biopsy, two days prior to evidence of blood engraftment in a patient who received an autologous hematopoietic stem cell transplantation (ASCT).

CASE REPORT
A 54-year-old man diagnosed with multiple myeloma received induc-

DISCUSSION
Our case illustrates that neutrophil tissue delivery was indeed present prior to myeloid engraftment as his ANC was zero on the day of the biopsy of the skin lesion that demonstrated neutrophils in the tissue.
Detection of ANC in this way is clearly not a replicable method of predicting early engraftment but does support the existing notion that marrow recovery occurs prior to the rising of an ANC level.
This incident also demonstrates that neutrophils mobilized to the site of inflammation, similar to the early delivery of neutrophils to the oral cavity. The presence of salivary neutrophils is in response to mucositis, a side effect of chemotherapy, which constitutes a common site of injury in this particular patient population [3]. However, there is evidence to support the rise of oral neutrophils in addition to blood neutrophils occurs by merit of inflammatory states not necessarily involving the oral cavity [4]. Of note, this patient was involved in the HBO clinical trial and was randomized to the interventional group, which may have affected the time to neutrophil recovery [5].
A variety of predictors of marrow recovery indicate that engraftment likely occurs earlier than the conventional evidence of an ANC level ≥500/µL. Examples of these markers include detection of neutrophils in oral mucosa, early monocyte recovery, hypophosphatemia, and measuring the immature reticulocyte population [6][7][8][9]. Their use has suggested that marrow recovery after HSCT likely occurs at least 2 days earlier than blood engraftment. Oral rinses have been shown to detect neutrophils at a range of 2-8 days earlier than neutrophils in the circulation [6,10,11]. While this is a noninvasive method, their collection may be limited by presence of oral mucositis and nausea [11]. Absolute monocyte count ≥100/µL has been suggested to antedate ANC by about 5 days [7,12]. The use of blood cell parameters (including volume, conductivity, and light scatter) showed earlier engraftment by approximately 4 days in both autologous and allogenic transplant groups, with the only difference between them being related to the volume of stem cells infused [12]. Hypophosphatemia (a drop in levels by 20%) is an electrolyte that can also reflect marrow recovery due to cell replication, although this is nonspecific and can be influenced by iatrogenic supplementation [7,9]. In this particular case, hypophosphatemia, specifically a drop of 47% from baseline occurred congruently with the evidence of tissue neutrophil delivery, monocyte recovery, and prior to ANC recovery. Immature reticulocyte fraction, a tool that reflects erythroid engraftment and therefore marrow recovery and may be the earliest indicator of marrow recovery, preceded ANC recovery in ASCT by 3-6 days [7,8].
Neutrophil repopulation is an essential milestone in the post-